1. Field of the Invention
The present invention relates to nucleic acid sequences and proteins involved in senescence and particularly, to nucleic acid sequences and proteins involved in cellular senescence and their use.
2. Description of the Related Art
The mechanism on senescence (also, called “aging”) was intensively studied and a variety of hypotheses were suggested. The hypothesis comprises (a) free radical theory of aging (Harman D, Proc. Natl. Acad. Sci., 78, 7124–7128 (1981)), (b) crosslinking theory of aging (Bjorksten J., J. Am. Geriatr Soc., 16, 408–423 (1968)), (c) mitochondrial theory of aging (Lee C M et al., Free Radic. Biol. Med., 22, 1259–1269 (1997); and Wallace D C et al., Biofactors, 7, 187–190 (1998)), and (d) genetic program theory of aging (Harley C B et al., Curr. Opin. Genet. Dev., 5, 249–255 (1995)).
Moreover, the senescence has been investigated in cellular level, i.e., cellular senescence. According to the investigation, senescent cell is characterized by (a) arrest of cell cycle at G1 phase, (b) diminished physiological functions (Goldstein, Science, 249:1129–1133 (1990); Campisi J., Cell, 84:497–500 (1996)), and (c) resistance to apoptotic-programmed-cell death (Wang E., Cancer Res., 55:2284–2292 (1995)).
A large variety of studies on cellular senescence have been made with human fibroblasts since the cells are considered to reflect a senescence phenomenon in individual level (Campisi J., Cell, 84:497–500(1996)).
Meanwhile, the patent applications related to nucleic acid and proteins associated with aging process, disclosed in WO 99/52929 and WO 01/23615.
As described above, a variety of theories have been proposed, there remains a need of more evident elucidation for cellular senescence, a need of specific biomarker for identifying senescent cell, and a need of biomolecule for modulating cellular senescence.
In particular, the prospect of reversing senescence and restoring normal physiological function has an importance in certain diseases associated with senescence, for example, Werner Syndrome and Hutchinson-Gilford Syndrome.
Throughout this application, various patents and publications are referenced and citations are provided in parentheses. The disclosure of these patents and publications in their entities are hereby incorporated by references into this application in order to more fully describe this invention and the state of the art to which this invention pertains.